On the road to creating an affordable master instrument

What talented young violinist has not dreamt of playing on a Stradivarius, that non plus ultra of the violin-maker's art? Unfortunately, of course, these instruments are rare, and well beyond the budget of most musicians. "Imitations" of similar tonal quality are therefore very sought-after, and the Empa researcher Francis Schwarze has managed to achieve this feat with the help of a Swiss violin maker. By treating the wood with Physisporinus vitreus, a white-rot fungus which attacks and destroys certain structures in spruce, he was able to create a material with extraordinarily good tonal qualities. So good in fact that the new "fungus violin" put its own role model in the shade. At a specialist conference in 2009 two of the new instruments were compared in a blind test to a Stradivarius and both the jury of experts and the conference audience judged their sound to better than that of the violin made by the Italian Master of Cremona.

Schwarze now intends to develop a standardized biotechnological process so that sufficient fungally-treated wood can be produced to make instruments in respectable numbers. This is the only way that would allow an industrial partner interested in the technology to manufacture the violins on a quasi-"mass-produced" basis. In order to create the necessary bridge between science and industry it is vital to develop technologies which offer potential partners significant commercial advantages. In this case this means standardizing the wood treatment parameters to such an extent that a specific tonal quality can be guaranteed. This is not an easy task to accomplish with a material such as wood which is subject to natural fluctuations in quality.

Generous support from the Walter Fischli Foundation

In the Walter Fischli Foundation the Empa scientist has found financial support which will enable the "fungal violin" project continue. Explaining why he decided to provide funding for Schwarze's work, Walter Fischli, who is co-founder of the biomedical company Actelion and an enthusiastic hobby violinist, says "In my opinion it would have been unforgivable to allow such an interesting project – one that so ideally links science and the art of violin making – to wither for lack of funding." Fischli hopes that the Empa specialists will finally uncover the secret of why violin makers such as Stradivarius and Guarnerius managed to make instruments of such fantastic quality around 1700. Their craftsmanship is, of course, one decisive and undisputed factor but it seems that the wood they used also played a vital role. "Using modern science to explain the technical details of the material properties is something I find enormously interesting," says Fischli.

Developing a standard wood treatment process in an interdisciplinary way

The project, which commenced at the beginning of September and will run for three years, is led by Iris Brémaud, a specialist in the field of tonal woods. The French scientist is responsible for ensuring that the treatment with the white rot fungi P. vitreus and Xylaria longipes optimally "ennobles" samples of spruce and maple woods. In addition she is already in contact with Michael Baumgartner, the renowned instrument maker from Basel. Under his guidance the "fungus violins" using the treated wood will be created.

Before Empa can take delivery of the first violin, however, numerous tests on both treated and untreated wood samples must be carried out. Experts are currently systematically measuring the density of the wood, the speed of sound in it and its acoustic attenuation. Specialists in the field of ultrasonics are developing methods to determine where the fungus was active and where not. Other scientists expert in optical measurement techniques are using their specialist methods to create images showing how sound is radiated by the different woods and also complete instruments. The final steps should involve collaborations with specialists of psychoacoustics to understand how musicians and listeners perceive these "mushroom violins."

Provided by EMPA

Fluorescent probes increase understanding of bacterium's electron transfer

These results mark another step toward understanding the cellular mechanisms that enable a bacterial protein-in this case, the cytochrome MtrC-to transfer electrons to minerals in soil, sediment, and subsurface materials. This new information contributes to understanding protein stability and electron transfer between cells and minerals, which is important for applications in synthetic biology such as biofuel production. The results were published in the journal Biochemistry.

Electron transfer by MtrC, an outer membrane cytochrome on S. oneidensis, can stabilize contaminants, mitigating their impact on the population and environment. However, scientists believe that gaining insight into the electron transfer mechanisms could also play a role in directing the bacterium toward biofuel production.

"Our goal is to define the role of these cytochromes in the metabolic switching between different terminal electron acceptors," said Dr. Thomas Squier, a PNNL biochemist and senior author of the publication. "The long-term goal is to understand the stability and targeting mechanisms important to synthetic biology applications involving, for example, chemical sensing between living cells and electronic detectors as well as the development of biofuel cells."

These findings don't just relate to Shewanella, though it was in this microbe where MtrC was first seen. They also apply to many other bacteria, such as E. coli, notes Squier.

"This research ties very well into looking at and understanding microbial communities as a whole," he added.

Measuring MtrC's environmental stability requires the ability to differentiate an immature protein from a mature protein after it is secreted and assembled on Shewanella's outer membrane. To do this, the scientists constructed complementary fluorescent probes to label MtrC. The highly charged carboxy-FlAsH (CrAsH) probe selectively labels mature MtrC only on the outer cell membrane, while the cell-permeable Fluorescein Arsenical Helix (FlAsH) probe labels all MtrC, including immature proteins within the cell.

More information: Xiong Y, et al. 2011. "Targeted Protein Degradation of Outer Membrane Decaheme Cytochrome MtrC Metal Reductase in Shewanella oneidensis MR-1 Measured Using Biarsenical Probe CrAsH-EDT2." Biochemistry 50(45):9738-9751 DOI: 10.1021/bi200602f

Provided by Pacific Northwest National Laboratory (news : web)

Shedding light on why it is so 'tough' to make healthier hot dogs

Anna M. Herrero and colleagues explain that some brands of sausage (frankfurters) have been reformulated with olive oil-in-water emulsion as a source of more healthful fat. With consumers gobbling up tens of billions of hot dogs annually, and the typical frankfurter packing 80 percent of its calories from fat, hot dogs have become a prime candidate for reformulation. Some hot dogs reformulated with vegetable oil develop an unpleasant chewy texture. Herrero's team set out to uncover the chemistry behind that change with an eye to guiding food companies to optimize low-fat sausage manufacture.

Using a laboratory instrument called an infrared spectrometer (IR spectrometer) they verified that sausages made with heart-healthy olive oil-in-water emulsion stabilized with casein were slightly tougher. However, when frankfurters were elaborated with an emulsion stabilized with a combination of casein and microbial transglutaminase (to help the oil blend in better) the sausage became much tougher. The IR spectrometer revealed that the proteins and fats in low-fat cooked derivates formulated with this stabilizer system as animal fat replacer showed weak lipid-protein interactions, which implies more physical entrapment of the emulsion within the meat matrix. This fact could explain why those sausages are tougher than the others.

More information: Infrared Study of Structural Characteristics of Frankfurters Formulated with Olive Oil-in-Water Emulsions Stabilized with Casein As Pork Backfat Replacer, J. Agric. Food Chem., Article ASAP. DOI: 10.1021/jf203941b

Abstract
This article reports an infrared spectroscopic (FT-IR) study on lipids and protein structural characteristics in frankfurters as affected by an emulsified olive oil stabilizing system used as a pork backfat replacer. The oil-in-water emulsions were stabilized with sodium caseinate, without (F/SC) and with microbial transglutaminase (F/SC+MTG). Proximate composition and textural characteristics were also evaluated. Frankfurters F/SC+MTG showed the highest (P < 0.05) hardness and lowest (P < 0.05) adhesiveness. These products also showed the lowest (P < 0.05) half-bandwidth of the 2922 cm–1 band, which could be related to the fact that the lipid chain was more orderly than that in the frankfurters formulated with animal fat and F/SC. The spectral results revealed modifications in the amide I band profile when the olive oil-in-water emulsion replaced animal fat. This fact is indicative of a greater content of aggregated intermolecular ß-sheets. Structural characteristics in both proteins and lipids could be associated with the specific textural properties of frankfurters.

Provided by American Chemical Society (news : web)

Researchers discover a mechanism of drug resistance

However, mycophenolic acid also poisons most microbes, which has had scientists wondering how molds that produce mycophenolic acid can grow in its presence. This general problem is only understood in a few cases. Understanding how some microbes resist high concentrations of antibiotics is important to designing new drugs and deciding how and when to prescribe existing drugs.

Xin Sun, a Ph.D. student in Biology Professor Liz Hedstrom’s laboratory, together with Bjarne Gram Hansen of the Technical University of Denmark, got down to the molecular level to unearth that answer for mycophenolic acid production. Their research was recently reported in The Journal of Biological Chemistry and the Biochemical Journal.

Every drug has a target — in this case a protein to which the drug binds, blocking its normal function.  In the case of mycophenolic acid, the target is the protein IMPDH, an enzyme found in every organism.  The faster an organism is growing, the more IMPDH it needs.  When an infection occurs, immune cells need to grow, so they produce more IMPDH.

Unlike most microbes, Penicillium have two copies of IMPDH.

“What Xin Sun did was to show that this second IMPDH is in fact resistant to mycophenolic acid,” says Hedstrom.  “What was puzzling is that you’d expect a change in the drug binding site, but here the drug binding site is identical in both sensitive and resistant targets. Instead, the underlying function of the second IMPDH has changed in clever and sophisticated ways so the drug is no longer effective.”

These findings also provide new insights into another scientific mystery, how antibiotic production evolved in the first place.  The team hypothesizes that Penicillium molds gained the second IMPDH through mutation (duplication), which allowed them to make small amounts of mycophenolic acid.  Over time, the second IMPDH evolved to become more resistant, allowing the mold to make more mycophenolic acid. 

Provided by Brandeis University (news : web)

Pharmacists crucial in plan for terrorist chemical weapons

Chemical weapons act on their victims through a number of mechanisms. They include nerve agents, chemicals that cause blistering (vesicants), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. With their knowledge of chemistry, microbiology, pharmacology, toxicology, and therapeutics, pharmacists are a valuable asset to health care facilities and government agencies planning for the unthinkable – a terrorist attack with chemical weapons.

In his article, clinical pharmacist and forensic pharmacologist Peter D. Anderson details the clinical effects chemical weapons, and their treatment. Nerve agents work by blocking the actions of acetyl cholinesterase (the chemistry involved is similar to how many pesticides kill). These toxins include sarin, tabun, VX, cyclosarin, and soman. Vesicants like sulfur mustard and lewisite produce blisters and damage the upper airways. Choking agents, which cause fluid to build up in the lungs (pulmonary edema), include phosgene and chlorine gas.

Incapacitating agents are temporary and "non-lethal," and include fentanyl and adamsite. Mace and pepper spray are familiar riot control methods. Blood agents include cyanide, which works by blocking oxidative phosphorylation in the body. Toxic industrial chemicals such as formaldehyde, hydrofluoric acid, and ammonia also merit consideration as terrorist weapons.

"Potential chemical weapons are in no way limited to the traditional agents that we think of as chemical weapons," Anderson explains.

The good news is that there are potential antidotes to these chemical agents, which can save lives if they are used quickly and correctly. Pharmacists need to work in their hospitals to prepare emergency plans, and with the pharmacy and therapeutic committees to stock for a potential chemical accident or terrorist attack. In the US, for example, The Centers for Disease Control and Prevention (CDC) maintains a Strategic National Stockpile of pharmaceuticals, medical equipment and supplies that can be sent in an emergency to any US state within 12 hours.

The threat from chemical agents may appear to be a symptom of our modern society, but the idea has been around since antiquity. Solon of Athens is said to have used hellebore roots (a purgative) to contaminate the water supply in the Pleistrus River during the Siege of Cirrha as long ago as 590 BC. Modern chemical warfare during World War I included the release by German soldiers of 150 tons of chlorine gas near Ypres, Belgium, and phosgene and nitrogen mustard also played a role in the conflict. Choking agents, vesicants, blood agents, and nerve gas joined the range of chemical weapons available by World War II. Even though conflicting nations produced these in large quantities, no major chemical weapon events occurred during World War II.

The Chemical Weapons Convention was finalized in 1993, prohibiting development, production, stockpiling, and use of chemical weapons. The treaty also mandated weapons destruction. 130 countries signed the convention (excluding Iraq and North Korea).

Although the article is about chemical weapons, Anderson emphasizes that pharmacists can also be a resource for biological, radiological and nuclear attacks as well as natural disasters.

More information: Emergency Management of Chemical Weapons Injuries by Peter D. Anderson is published in the Journal of Pharmacy Practice. The article is free to access here: http://jpp.sagepub … ull.pdf+html

Provided by SAGE Publications